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Although significant progress has been made in understanding the cortical correlates underlying balance control, these studies focused on a single task, limiting the ability to generalize the findings. Different balance tasks may elicit cortical activations in the same regions but show different levels of activation because of distinct underlying mechanisms. In this study, twenty young, neurotypical adults were instructed to maintain standing balance while the standing support surface was either translated or rotated. The differences in cortical activations in the frontocentral region between these two widely used tasks were examined using electroencephalography (EEG). Additionally, the study investigated whether transcranial magnetic stimulation could modulate these cortical activations during the platform translation task. Higher delta and lower alpha relative power were found over the frontocentral region during the platform translation task when compared to the platform rotation task, suggesting greater engagement of attentional and sensory integration resources for the former. Continuous theta burst stimulation over the supplementary motor area significantly reduced delta activity in the frontocentral region but did not alter alpha activity during the platform translation task. The results provide a direct comparison of neural activations between two commonly used balance tasks and are expected to lay a strong foundation for designing neurointerventions for balance improvements with effects generalizable across multiple balance scenarios. [ABSTRACT FROM AUTHOR]

AbstractAim of the StudyMaterials and MethodsConclusionThis study aimed to present a case of intermittent theta-burst stimulation (iTBS) and continuous theta-burst stimulation (cTBS) dual stimulation for the treatment of postpartum obsessive-compulsive disorder (OCD). The objective was to provide a referenceable therapy in cases where medication and psychotherapy treatment are not preferred or contraindicated. This case further emphasized the importance of non-invasive neuromodulation techniques in improving the condition of postpartum OCD patients.A 32-year-old female was diagnosed with OCD 2 months after delivery. The patient refused to take medication and psychotherapy due to concerns that it would interfere with the infant’s breastfeeding. Subsequently, a 2-week combined iTBS and cTBS treatment was carried out. The patient’s obsessive-compulsive symptoms, anxiety, and depression improved. There were no significant adverse effects during the treatment, and the treatment effect remained 2 weeks after the end of the treatment.This clinical case provides evidence that the combined iTBS and cTBS treatment can potentially effectively alleviate obsessive-compulsive symptoms in the short term. Notably, this therapeutic approach may offer a promising solution for postpartum OCD patients, as it addresses practical concerns such as medication safety for breastfeeding mothers and the specific needs of this population. To further establish the efficacy of this combined therapy, future randomized controlled trials with large samples and long-term follow-up are warranted to validate its therapeutic potential. [ABSTRACT FROM AUTHOR]

Studies using magnetic brain stimulation indicate the involvement of somatosensory regions in the acquisition and retention of newly learned movements. Recent work found an impairment in motor memory when retention was tested shortly after the application of continuous theta-burst stimulation (cTBS) to the primary somatosensory cortex, compared with stimulation of the primary motor cortex or a control zone. This finding that the somatosensory cortex is involved in motor memory retention whereas the motor cortex is not, if confirmed, could alter our understanding of human motor learning. It would indicate that plasticity in sensory systems underlies newly learned movements, which is different than the commonly held view that adaptation learning involves updates to a motor controller. Here we test this idea. Participants were trained in a visuomotor adaptation task, with visual feedback gradually shifted. Following adaptation, cTBS was applied either to M1, S1, or an occipital cortex control area. Participants were tested for retention 24 h later. It was observed that S1 stimulation led to reduced retention of prior learning, compared with stimulation of M1 or the control area (with no significant difference between M1 and control). In a further control, cTBS was applied to S1 following training with unrotated feedback, in which no learning occurred. This had no effect on movement in the retention test indicating the effects of S1 stimulation on movement are learning specific. The findings are consistent with the S1 participation in the encoding of learning-related changes to movements and in the retention of human motor memory. [ABSTRACT FROM AUTHOR]

Music represents a salient stimulus for the brain with two key features: pitch and rhythm. Few data are available on cognitive analysis of music listening in musically naïve healthy participants. Beyond auditory cortices, neuroimaging data showed the involvement of prefrontal cortex in pitch and of cerebellum in rhythm. The present study is aimed at investigating the role of prefrontal and cerebellar cortices in both pitch and rhythm processing. The performance of fifteen participants without musical expertise was investigated in a listening discrimination task. The task required to decide whether two eight-element melodic sequences were equal or different according to pitch or rhythm characteristics. Before the task, we applied a protocol of continuous theta burst transcranial magnetic stimulation interfering with the activity of the left cerebellar hemisphere (lCb), right inferior frontal gyrus (rIFG), or vertex (Cz-control site), in a within cross-over design. Our results showed that participants were more accurate in pitch than rhythm tasks. Importantly, the reaction times were slower following rIFG or lCb stimulations in both tasks. Notably, frontal and cerebellar stimulations did not induce any motor effect in right and left hand. The present findings point to the role of the fronto-cerebellar network in music processing with a single mechanism for both pitch and rhythm patterns. [ABSTRACT FROM AUTHOR]

Recent studies have indicated somatosensory cortex involvement in motor learning and retention. However, the nature of its contribution is unknown. One possibility is that the somatosensory cortex is transiently engaged during movement. Alternatively, there may be durable learning-related changes which would indicate sensory participation in the encoding of learned movements. These possibilities are dissociated by disrupting the somatosensory cortex following learning, thus targeting learning-related changes which may have occurred. If changes to the somatosensory cortex contribute to retention, which, in effect, means aspects of newly learned movements are encoded there, disruption of this area once learning is complete should lead to an impairment. Participants were trained to make movements while receiving rotated visual feedback. The primary motor cortex (M1) and the primary somatosensory cortex (S1) were targeted for continuous theta-burst stimulation, while stimulation over the occipital cortex served as a control. Retention was assessed using active movement reproduction, or recognition testing, which involved passive movements produced by a robot. Disruption of the somatosensory cortex resulted in impaired motor memory in both tests. Suppression of the motor cortex had no impact on retention as indicated by comparable retention levels in control and motor cortex conditions. The effects were learning specific. When stimulation was applied to S1 following training with unrotated feedback, movement direction, the main dependent variable, was unaltered. Thus, the somatosensory cortex is part of a circuit that contributes to retention, consistent with the idea that aspects of newly learned movements, possibly learning-updated sensory states (new sensory targets) which serve to guide movement, may be encoded there. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) can modulate a targeted brain region to assess whether that region is involved in a cognitive process. When TMS is employed in cognitive neuroscience, participants are typically healthy volunteers, and the technique is described as noninvasive. However, TMS parameters can be set such that stimulation produces long-lasting effects. Critically, TMS effects that have any possibility of lasting beyond a participant's time in the lab are potentially harmful. In this editorial, evidence is considered that indicates a 20-Hz multi-day TMS protocol has long-lasting effects, and a continuous theta-burst stimulation protocol needs further testing before it is deemed noninvasive. The following guidelines are provided for TMS protocol evaluation: 1) Effects must be shown to completely dissipate before participants leave the lab by testing well beyond the expected duration. 2) Participants should complete a cognitive test battery before TMS and after the effects are expected to dissipate. 3) Protocols should not be employed that produce effects lasting longer than the time in the lab. 4) The number of participants should ensure error bars are small, and results generalize to the population. 5) Results should be assessed at the group and individual-participant level, and effects should dissipate for every participant. 6) Bayesian analysis should be conducted to evaluate evidence in favor of the null hypothesis. 7) Effects should be assessed in multiple cortical regions. It is hoped that these guidelines will be employed to ensure the continued use of TMS as a valuable tool in the field of cognitive neuroscience. [ABSTRACT FROM AUTHOR]

Cryptophanes show different conformations in solution and solid state depending upon various factors, such as the length of connecting linkers, medium, and nature of the incoming guest molecule(s). A cyclotriguaiacylenes (CTG) based cryptophane molecule was synthesized using click chemistry containing three triazole linkers and studied as well. This molecule shows two conformations, out‐out crown‐crown (CC), and out‐in CC, in the presence or absence of guest molecule(s), as studied both in solution and solid state. The out‐in CC, in which both CTG fragments are in crown conformation with one crown sitting above the other, could be obtained by slow escape of the trapped acetone molecules from out‐out CC in solid state. This transformation could be obtained through a single‐crystal‐to‐single‐crystal (SCSC) transformation from a large volume out‐out CC to a smaller volume out‐in CC conformation which is also supported by density functional theory calculations. [ABSTRACT FROM AUTHOR]

Background: Although in 2017 a repetitive transcranial magnetic stimulation (rTMS) protocol received Food and Drug Administration approval for the first time for the treatment of obsessive–compulsive disorder (OCD), which neural target and which protocol should be used for OCD are still debated. The aim of the present study was to perform a systematic review and meta-analysis of the available open and sham-controlled trials. Methods: The primary analysis included a pairwise meta-analysis (over 31 trials), and then subgroup analyses were performed for each targeted brain area. Meta-regression analyses explored the possible moderators of effect size. Results: The pairwise meta-analysis showed a significant reduction in OCD symptoms following active rTMS (g = −0.45 [95%CI: −0.62, −0.29]) with moderate heterogeneity (I2 = 34.9%). Subgroup analyses showed a significant effect of rTMS over the bilateral pre-SMA (supplementary motor area), the DLPFC (dorsolateral prefrontal cortex), the ACC/mPFC (anterior cingulate cortex and medial prefrontal cortex), and the OFC (orbitofrontal cortex). No moderators of the effect size emerged. Conclusions: TMS of several brain targets represents a safe and effective treatment option for OCD patients. Further studies are needed to help clinicians to individualize TMS protocols and targets for each patient. [ABSTRACT FROM AUTHOR]

Intro: Aggressive behavior represents a significant public health issue, with relevant social, political, and security implications. Non-invasive brain stimulation (NIBS) techniques may modulate aggressive behavior through stimulation of the prefrontal cortex. Aims: To review research on the effectiveness of NIBS to alter aggression, discuss the main findings and potential limitations, consider the specifics of the techniques and protocols employed, and discuss clinical implications. Methods: A systematic review of the literature available in the PubMed database was carried out, and 17 randomized sham-controlled studies investigating the effectiveness of NIBS techniques on aggression were included. Exclusion criteria included reviews, meta-analyses, and articles not referring to the subject of interest or not addressing cognitive and emotional modulation aims. Conclusions: The reviewed data provide promising evidence for the beneficial effects of tDCS, conventional rTMS, and cTBS on aggression in healthy adults, forensic, and clinical samples. The specific stimulation target is a key factor for the success of stimulation on aggression modulation. rTMS and cTBS showed opposite effects on aggression compared with tDCS. However, due to the heterogeneity of stimulation protocols, experimental designs, and samples, we cannot exclude other factors that may play a confounding role. [ABSTRACT FROM AUTHOR]

Visual hallucinations after central or peripheral impairment, commonly called Charles Bonnet syndrome, are often highly distressing and with few available treatment options. Here we report a case where an adolescent developed severely distressing visual hallucinations after hypoxic damage to the occipital cortex following a suicide attempt. The patient received active and sham occipital continuous theta-burst stimulation (cTBS) in a single-case experimental research design and a subsequent open phase, to evaluate cTBS as a Charles Bonnet treatment. The visual hallucinations seemed to decrease more during active than sham cTBS in the blind phase, and in the following week of repeated five daily treatments they almost disappeared. A normalization of increased activity in the lateral visual network after cTBS was observed on a functional magnetic resonance imaging resting-state analysis compared with 42 healthy controls. Visual evoked potentials stayed largely unchanged both in the sham-controlled blind phase and the subsequent open phase. During the two weeks after the open phase with repeated cTBS sessions, the visual hallucinations gradually reappeared and almost returned to the baseline level. Our findings suggest that active cTBS over the primary visual cortex can reduce visual hallucinations through modulation of downstream visual regions, though the effect is temporally limited. [ABSTRACT FROM AUTHOR]

As we move through an environment, we update positions of our body relative to other objects, even when some objects temporarily or permanently leave our field of view—this ability is termed egocentric spatial updating and plays an important role in everyday life. Still, our knowledge about its representation in the brain is still scarce, with previous studies using virtual movements in virtual environments or patients with brain lesions suggesting that the precuneus might play an important role. However, whether this assumption is also true when healthy humans move in real environments where full body-based cues are available in addition to the visual cues typically used in many VR studies is unclear. Therefore, in this study we investigated the role of the precuneus in egocentric spatial updating in a real environment setting in 20 healthy young participants who underwent two conditions in a cross-over design: (a) stimulation, achieved through applying continuous theta-burst stimulation (cTBS) to inhibit the precuneus and (b) sham condition (activated coil turned upside down). In both conditions, participants had to walk back with blindfolded eyes to objects they had previously memorized while walking with open eyes. Simplified trials (without spatial updating) were used as control condition, to make sure the participants were not affected by factors such as walking blindfolded, vestibular or working memory deficits. A significant interaction was found, with participants performing better in the sham condition compared to real stimulation, showing smaller errors both in distance and angle. The results of our study reveal evidence of an important role of the precuneus in a real-environment egocentric spatial updating; studies on larger samples are necessary to confirm and further investigate this finding. [ABSTRACT FROM AUTHOR]

The appearance of a salient stimulus evokes a series of orienting responses including saccades and pupil size to prepare the body for appropriate action. The midbrain superior colliculus (SC) that receives critical control signals from the frontal eye field (FEF) is hypothesized to coordinate all components of orienting. It has shown recently that the FEF, together with the SC, is also importantly involved in the control of pupil size, in addition to its well‐documented role in eye movements. Although the role of the FEF in pupil size is demonstrated in monkeys, its role in human pupil responses and the coordination between pupil size and saccades remains to be established. Through applying continuous theta‐burst stimulation over the right FEF and vertex, we investigated the role of the FEF in human pupil and saccade responses evoked by a salient stimulus, and the coordination between pupil size and saccades. Our results showed that neither saccade reaction times (SRT) nor pupil responses evoked by salient stimuli were modulated by FEF stimulation. In contrast, the correlation between pupil size and SRTs in the contralateral stimulus condition was diminished with FEF stimulation, but intact with vertex stimulation. Moreover, FEF stimulation effects between saccade and pupil responses associated with salient stimuli correlated across participants. This is the first transcranial magnetic stimulation (TMS) study on the pupil orienting response, and our findings suggest that human FEF was involved in coordinating pupil size and saccades, but not involved in the control of pupil orienting responses. [ABSTRACT FROM AUTHOR]

• A model of motor-evoked potential formation gives a realistic electromyogram in response to TMS. • The model reproduces effects of short-interval intracortical inhibition, intracortical facilitation and long-interval intracortical inhibition. • A link between existing neural field modeling and realistic outcome measures of TMS is provided. To develop a population-based biophysical model of motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS). We combined an existing MEP model with population-based cortical modeling. Layer 2/3 excitatory and inhibitory neural populations, modeled with neural-field theory, are stimulated with TMS and feed layer 5 corticospinal neurons, which also couple directly but weakly to the TMS pulse. The layer 5 output controls mean motoneuron responses, which generate a series of single motor-unit action potentials that are summed to estimate a MEP. A MEP waveform was generated comparable to those observed experimentally. The model captured TMS phenomena including a sigmoidal input–output curve, common paired pulse effects (short interval intracortical inhibition, intracortical facilitation, long interval intracortical inhibition) including responses to pharmacological interventions, and a cortical silent period. Changes in MEP amplitude following theta burst paradigms were observed including variability in outcome direction. The model reproduces effects seen in common TMS paradigms. The model allows population-based modeling of changes in cortical dynamics due to TMS protocols to be assessed in terms of changes in MEPs, thus allowing a clear comparison between population-based modeling predictions and typical experimental outcome measures. [ABSTRACT FROM AUTHOR]

While much progress has been made in how brain organization supports language function, the language network's ability to adapt to immediate disturbances by means of reorganization remains unclear. The aim of this study was to examine acute reorganizational changes in brain activity related to conceptual and lexical retrieval in unimpaired language production following transient disruption of the left middle temporal gyrus (MTG). In a randomized single‐blind within‐subject experiment, we recorded the electroencephalogram from 16 healthy participants during a context‐driven picture‐naming task. Prior to the task, the left MTG was perturbed with real continuous theta‐burst stimulation (cTBS) or sham stimulation. During the task, participants read lead‐in sentences creating a constraining (e.g., "The farmer milks the") or nonconstraining context (e.g., "The farmer buys the"). The last word was shown as a picture that participants had to name (e.g., "cow"). Replicating behavioral studies, participants were overall faster in naming pictures following a constraining relative to a nonconstraining context, but this effect did not differ between real and sham cTBS. In contrast, real cTBS increased overall error rates compared to sham cTBS. In line with previous studies, we observed a decrease in alpha‐beta (8–24 Hz) oscillatory power for constraining relative to nonconstraining contexts over left temporal–parietal cortex after participants received sham cTBS. However, following real cTBS, this decrease extended toward left prefrontal regions associated with both domain‐general and domain‐specific control mechanisms. Our findings provide evidence that immediately after perturbing the left MTG, the lexical‐semantic network is able to quickly reconfigure, also recruiting domain‐general regions. [ABSTRACT FROM AUTHOR]

The cerebellum is implicated in the pathophysiology of numerous movement disorders, which makes it an attractive target for noninvasive neurostimulation. Continuous theta burst stimulation (cTBS) can induce long lasting plastic changes in human brain; however, the efficacy of different simulation protocols has not been investigated at the cerebellum. Here, we compare a traditional 50-Hz and a modified 30-Hz cTBS protocols at modulating cerebellar activity in healthy subjects. Seventeen healthy adults participated in two testing sessions where they received either 50-Hz (cTBS50) or 30-Hz (cTBS30) cerebellar cTBS. Cerebellar brain inhibition (CBI), a measure of cerebello-thalamocortical pathway strength, and motor evoked potentials (MEP) were measured in the dominant first dorsal interosseous muscle before and after (up to ~ 40 min) cerebellar cTBS. Both cTBS protocols induced cerebellar depression, indicated by significant reductions in CBI (P < 0.001). No differences were found between protocols (cTBS50 and cTBS30) at any time point (P = 0.983). MEP amplitudes were not significantly different following either cTBS protocol (P = 0.130). The findings show cerebellar excitability to be equally depressed by 50-Hz and 30-Hz cTBS in heathy adults and support future work to explore the efficacy of different cerebellar cTBS protocols in movement disorder patients where cerebellar depression could provide therapeutic benefits. [ABSTRACT FROM AUTHOR]

Highlights • Continuous theta burst stimulation (cTBS) is a relatively new neuromodulation technique that requires further validation. • Across three studies cTBS targeting the left dlPFC revealed reliable attenuating effects on executive functions. • However, this effect was not universal in that 61.8% of participants showed the expected response. • cTBS effects were more pronounced for those with stronger baseline executive function performance. Abstract Despite the increasing use of continuous theta burst (cTBS) protocols targeting the prefrontal cortex in clinical and research settings, very little is known regarding the interindividual factors that influence the magnitude and duration of cTBS aftereffects. The few existing studies have predominantly focussed on motor and corticospinal excitability, and the applicability of such findings to prefrontal modulation remains unclear. The current investigation aggregated published data from our laboratory to (1) assess the reproducibility of the effects of cTBS targeting the left dorsolateral prefrontal cortex (dlPFC) on executive function task performance, and (2) determine which factors are associated with individual differences in cTBS responsivity. Data from 76 healthy young adult female participants aged 19–26 (M = 20.6; SD = 1.6) were included in the analyses. Significant attenuations in executive function task performance from baseline were observed following active cTBS. However, these effects were not totally universal in that cTBS-induced attenuation of executive functions was observed in 61.8% of participants (i.e., responders). In addition, baseline task performance was a significant predictor of the magnitude of the cTBS-induced change in task performance in that cTBS effect was larger for individuals with higher baseline executive control abilities than those with lower abilities. Together, these data provide a quantitative estimate of the degree to which healthy participants may vary in the responsiveness to prefrontal cTBS, and potential moderating factors. [ABSTRACT FROM AUTHOR]

Regulation of food cravings is thought to be critical for modulating eating behavior, yet we do not fully understand the mechanisms by which cognitive control operates in the eating context. The current study combined rTMS and EEG paradigms to examine the causal role of the left dorsolateral prefrontal cortex (dlPFC) in modulating visceral and behavioral responses to high calorie foods, and the mediational mechanisms underlying this relation. 28 right-handed female participants received both active and sham continuous theta burst stimulation (cTBS; a rTMS variant used to decrease cortical activity) targeting the left dlPFC in a counterbalanced order. Prior to and following each stimulation session participants completed a flanker and food-cue presentation (high and low calorie food) task. Following cTBS participants had the opportunity to consume both high and low calorie foods during a taste test. Findings revealed a reliable effect of cTBS on food consumption, such that participants selectively ingested significantly more calories from appetitive calorie dense snack foods following active relative to sham cTBS; this effect did not translate to control (low calorie) food consumption. In addition, attenuation of dlPFC activity resulted in the significant increase in N2 amplitude and P3b latency to incongruent flanker trials, and the selective significant increase in the P3a amplitude to and P3a amplitude bias for high calorie food stimuli. Results from the parallel mediation analysis revealed that only the indirect effect of flanker task performance was significant; the indirect effects of stimulation induced changes in the P3 bias for high calorie foods, the urge to consume high calorie foods, and the general liking ratings for high calorie foods were not significant. These findings confirm the causal role of the left dlPFC in the modulation of calorie dense food consumption via inhibitory control capacity. [ABSTRACT FROM AUTHOR]

In the context of hedonic (over-)eating the ventral tegmental area (VTA) as a core part of the dopaminergic reward system plays a central role in coding incentive salience of high-caloric food. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate whether transcranial magnetic theta-burst stimulation (TBS) over the right mid-ventrolateral prefrontal cortex (mid-VLPFC) can induce modulation of calorie-sensitive brain activation in the VTA. The prefrontal location for TBS had been predetermined by seed-based resting-state fMRI with a functionally defined portion of the VTA serving as seed region obtained from an independent second fMRI experiment. In a sample of 15 healthy male participants, modulation of calorie-sensitive VTA activation did not significantly differ between the two TBS protocols. Comparisons with baseline revealed that both TBS protocols significantly affected calorie-sensitive neural processing of the mid-VLPFC in a rather similar way. In the VTA significant modulation of calorie-sensitive activation was observed after continuous TBS, whereas the modulatory effect of intermittent TBS was less reliable but also associated with a decrease of activation for high-caloric food images. Neurostimulation of right mid-VLPFC is suggestive as a main entry point of downstream signal changes for high- and low-caloric food cues that could enforce a shift in valuating stimuli of initially different incentive salience. [ABSTRACT FROM AUTHOR]

Prefrontal cortex (PFC) plays an important role in emotional processing and therefore is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) in clinical trials, especially in the treatment of emotional disorders. As an approach to enhance the effectiveness of rTMS, continuous theta burst stimulation (cTBS) has been demonstrated to be efficient and safe. However, it is unclear how cTBS affects brain processes related to emotion. In particular, psychophysiological studies on the underlying neural mechanisms are sparse. In the current study, we investigated how the cTBS influences emotional processing when applied over the right PFC. Participants performed an emotion recognition Go/NoGo task, which asked them to select a GO response to either happy or fearful faces after the cTBS or after sham stimulation, while 64-channel electroencephalogram (EEG) was recorded. EEG oscillation was examined using event-related spectral perturbation (ERSP) in a time-interval between 170 and 310 ms after face stimuli onset. In the sham group, we found a significant difference in the alpha band between response to happy and fearful stimuli but that effect did not exist in the cTBS group. The alpha band activity at the scalp was reduced suggesting the excitatory effect at the brain level. The beta and gamma band activity was not sensitive to cTBS intervention. The results of the current study demonstrate that cTBS does affect emotion processing and the effect is reflected in changes in EEG oscillations in the alpha band specifically. The results confirm the role of prefrontal cortex in emotion processing. We also suggest that this pattern of cTBS results elucidates mechanisms by which mood improvement in depressive disorders is achieved using cTBS intervention. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation and is thought to induce more rapid and longer-lasting effects on synaptic plasticity than conventional repetitive transcranial magnetic stimulation protocols. TBS is being used as an investigational and more recently as a therapeutic tool. The purpose of this review is to describe and discuss the studies that have evaluated the safety and efficacy of this technique in the treatment of various psychiatric disorders such as depression, schizophrenia, obsessive-compulsive disorder, Tourette's disorder, nicotine and cocaine addiction, and pathological gambling. Studies have reported mild adverse effects but no cases of seizures or mania. Despite the fact that studies were heterogeneous in terms of design and results, some of them are promising mostly for treatment-resistant depression and auditory hallucinations. Future well-designed sham-controlled studies are needed to confirm the long-term safety and efficacy of TBS in the treatment of such conditions. [ABSTRACT FROM AUTHOR]

The use of cerebellar repetitive transcranial magnetic stimulation has been attempted for perturbing reflexive and voluntary eye movements, but discrepancies are seen between the results of distinct studies possibly due to the different stimulation sites, intensities, and paradigms. We describe the after effects of 20 and 40 s continuous Theta Burst Stimulation (cTBS) as compared to sham stimulation, applied over the lateral cerebellar vermis and paravermis on Reflexive Saccades (RS) and Smooth Pursuit (SP) eye movements, recorded in the 30 min following stimulation. The experiments were carried out in eight healthy volunteers, and eye movements were recorded monocularly with video-oculography. The 40 s cTBS significantly increased the amplitude of ipsilateral RS and the acceleration of the ipsilateral SP, and this effect was detectable all over the 30-min recording period; 40 s cTBS did not modify the other parameters, namely the peak velocity, the duration and the latency of RS, and the latency and the velocity of SP. The 20 s cTBS was ineffective on all RS and SP parameters. Finally, we detected a significant quite-linear reduction of RS peak velocity over time, but this was independent from cTBS and was probably caused by fatigue. The effects of 40 s cTBS in our experiments mimic the disorder of ocular motility in Wallenberg's syndrome and could result from functional impairment of cerebellopontine pathways. This effect lasts 30 min at least, and can provide a useful framework for adaptive ocular motor studies. [ABSTRACT FROM AUTHOR]

Time perception in the millisecond and second ranges is thought to be processed by different neural mechanisms. However, whether there is a sharp boundary between these ranges and whether they are implemented in the same, overlapped or separate brain areas is still not certain. To probe the role of the right dorsolateral prefrontal cortex (dlPFC), the right supplementary motor area (SMA), and the cerebellum on time perception, we temporarily altered their activity on healthy volunteers on separate sessions using transcranial magnetic stimulation with the continuous Theta Burst Stimulation (cTBS) protocol. A control session was reserved for the stimulation of the primary somatosensory cortex (S1). Before and after stimulation, participants were tested on a temporal categorization task using intervals in the hundreds and thousands of milliseconds ranges, as well as on a pitch categorization task which was used as a further control. We then looked for changes in the Relative Threshold and the Constant Error, which, respectively, reflect participants’ sensitivity to interval duration and their accuracy at setting an interval that acts as a boundary between categories. We found that after cTBS in all of the studied regions, the Relative Threshold, but not the Constant Error, was affected and only when hundreds of milliseconds intervals were being categorized. Categorization of thousands of milliseconds intervals and of pitch was not affected. These results suggest that the fronto-cerebellar circuit is particularly involved in the estimation of intervals in the hundreds of milliseconds range. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) is a common condition associated with a variety of nervous system diseases, and has a negative impact on emotional and cognitive function. Continuous theta burst stimulation (cTBS) is known to improve cognition and emotion function in normal situations as well as in various types of dysfunction, but the mechanism remains unknown. We used two-photon in vivo imaging to explore the effect of cTBS on glymphatic pathway clearance in normal and SD C57BL/6J mice. Aquaporin-4 (AQP4) polarization was detected by immunofluorescence. Anxiety-like behaviors was measured using open field tests. We found that SD reduced influx efficiency along the peri-vascular space (PVS), disturbed AQP4 polarization and induced anxiety-like behaviors. CTBS significantly attenuated the decrease in efficiency of solute clearance usually incurred with SD, restored the loss of AQP4 polarization and improved anxiety-like behavior in SD animals. Our results implied that cTBS had the potential to protect against neuronal dysfunction induced by sleep disorders. [ABSTRACT FROM AUTHOR]

Despite the increasing use of functional connectivity (FC) studies in fundamental and clinical research, the link between FC and behavior is still poorly understood. To test the hypothesis that artificial modulation of FC correlates with changes in behavior in a quantitative manner, we performed behavioral and resting state fMRI experiments in monkeys while perturbing, offline, the frontal eye fields (FEF) using unilateral continuous theta burst transcranial magnetic stimulation (FEF-cTBS). Stimulation of left and right FEF caused remarkably specific decreases in FC, which were symmetric for intra-hemispheric and asymmetric for inter-hemispheric FC. Surprisingly, FEF-cTBS improved the performance and compensated intrinsic choice biases in saccadic behavior of four monkeys, independent of the initial bias direction. Moreover, the direction of the stimulation-induced effects on both behavior (i.e. bias compensation) and FC (i.e. decrease) were independent of the stimulated hemisphere, while their magnitude depended on the side of stimulation, choice bias and monkey. Overall, the naturally-occurring saccade biases determined the FC changes following FEF-cTBS. Finally, we showed that the average decreases in FC in the FEF network induced by cTBS can be used to predict, with high specificity, both the direction (opposite to the saccadic biases) and the magnitude of the shift in saccadic choice preference relative to the unperturbed state. To reconcile the apparent contradiction between improved performance and bias compensation vs. decrease in functional connectivity, we propose that the main functional consequences of FEF-cTBS relate to adjusting inter-hemispheric imbalances. [ABSTRACT FROM AUTHOR]

Microsaccades that occur during periods of fixation are modulated by various cognitive processes and have an impact on visual processing. A network of brain areas is involved in microsaccade generation, including the superior colliculus and frontal eye field (FEF) which are involved in modulating microsaccade rate and direction after the appearance of a visual cue (referred to as microsaccade cueing modulation). Although the neural mechanisms underlying microsaccade cueing modulations have been demonstrated in monkeys, limited research has investigated a causal role of these areas in humans. By applying continuous theta-burst transcranial magnetic stimulation (cTBS) over the right FEF and vertex, we investigated the role of human FEF in modulating microsaccade responses after the appearance of a visual target in a visual- and memory-delay saccade task. After target appearance, microsaccade rate was initially suppressed but then increased in both cTBS conditions. More importantly, in the visual-delay task, microsaccades after target appearance were directed to the ipsilateral side more often with FEF, compared to vertex stimulation. Moreover, microsaccades were directed towards the target location, then to the opposite location of the target in both tasks, with larger effects in the visual-, compared to, memory-delay task. This microsaccade direction modulation was delayed after FEF stimulation in the memory-delay task. Overall, some microsaccade cueing modulations were moderately disrupted after FEF cTBS, suggesting a causal role for involvement of the human FEF in microsaccade generation after presentation of salient stimuli. [ABSTRACT FROM AUTHOR]

Control of body balance relies on the integration of multiple sensory modalities. Lightly touching an earth-fixed reference augments the control of body sway. We aimed to advance the understanding of cortical integration of an afferent signal from light fingertip contact (LT) for the stabilisation of standing body balance. Assuming that right-hemisphere Posterior Parietal Cortex (rPPC) is involved in the integration and processing of touch for postural control, we expected that disrupting rPPC would attenuate any effects of light touch. Eleven healthy right-handed young adults received continuous Theta Burst Stimulation over the left- and right-hemisphere PPC with sham stimulation as an additional control. Before and after stimulation, sway of the blindfolded participants was assessed in Tandem-Romberg stance with and without haptic contact. We analysed sway in terms of the variability of Centre-of-Pressure (CoP) rate of change as well as Detrended Fluctuation Analysis of CoP position. Light touch decreased sway variability in both directions but showed direction-specific changes in its dynamic complexity: a positive increase in complexity in the mediolateral direction coincided with a reduction in the anteroposterior direction. rPPC disruption affected the control of body sway in two ways: first, it led to an overall decrease in sway variability irrespective of the presence of LT; second, it reduced the complexity of sway with LT at the contralateral, non-dominant hand. We speculate that rPPC is involved in the active exploration of the postural stability state, with utilisation of LT for this purpose if available, by normally inhibiting mechanisms of postural stiffness regulation. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the functional contribution of the human primary motor cortex (M1) to motor decisions. Continuous theta burst stimulation (cTBS) was used to alter M1 activity while participants performed a decision-making task in which the reward associated with the subjects’ responses (right hand finger movements) depended on explicit and implicit value-based rules. Subjects performed the task over two consecutive days and cTBS occurred in the middle of Day 2, once the subjects were just about to implement implicit rules, in addition to the explicit instructions, to choose their responses, as evident in the control group (cTBS over the right somatosensory cortex). Interestingly, cTBS over the left M1 prevented subjects from implementing the implicit value-based rule while its implementation was enhanced in the group receiving cTBS over the right M1. Hence, cTBS had opposite effects depending on whether it was applied on the contralateral or ipsilateral M1. The use of the explicit value-based rule was unaffected by cTBS in the three groups of subject. Overall, the present study provides evidence for a functional contribution of M1 to the implementation of freshly acquired implicit rules, possibly through its involvement in a cortico-subcortical network controlling value-based motor decisions. [ABSTRACT FROM AUTHOR]

How motion and sensory inputs are combined to assess an object's stiffness is still unknown. Here, we provide evidence for the existence of a stiffness estimator in the human posterior parietal cortex (PPC). We showed previously that delaying force feedback with respect to motion when interacting with an object caused participants to underestimate its stiffness. We found that applying theta-burst transcranial magnetic stimulation (TMS) over the PPC, but not the dorsal premotor cortex, enhances this effect without affecting movement control. Weexplain this enhancement as an additional lag in force signals. This is the first causal evidence that thePPCis not only involved in motion control, but also has an important role in perception that is disassociated from action. We provide a computational model suggesting that the PPC integrates position and force signals for perception of stiffness and that TMS alters the synchronization between the two signals causing lasting consequences on perceptual behavior. [ABSTRACT FROM AUTHOR]

The present study investigated the role of the precuneus in memory encoding of abstract and concrete words, with the combination of functional Magnetic Resonance Imaging (fMRI) and continuous Theta Burst Stimulation (cTBS) techniques. The memory encoding process was scanned in the fMRI to detect the regions of interest for the difference in memory formation of these two types of words. The real and sham cTBS stimulations were applied over the left precuneus. The fMRI results showed that the left precuneus was deactivated for the memory encoding of both types of words, with concrete words inducing significantly more deactivation. The cTBS stimulation over the left precuneus significantly reduced the reaction time of retrieval of abstract words but not concrete words. It is concluded that precuneus plays a role in modulating the abstract but not the concrete verbal memory encoding. • This study examines the role of precuneus in verbal episodic memory with combination of fMRI and cTBS. • The precuneus was deactivated for the episodic memory encoding of abstract and concrete words. • The precuneus was deactivated significantly less for the episodic encoding of abstract words than that of the concrete words. • The cTBS stimulation over precuneus significantly reduced the reaction time of retrieval of abstract words instead of concrete words. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the intensity of transcranial magnetic stimulation (TMS) used to probe changes in corticospinal excitability influences the measured plasticity response to theta burst stimulation (TBS) of the human primary motor cortex. Methods: Motor evoked potential (MEP) input/output (I/O) curves were recorded before and following continuous TBS (cTBS) (Experiment 1; n = 18) and intermittent TBS (iTBS) (Experiment 2; n = 18). Results: The magnitude and consistency of MEP depression induced by cTBS was greatest when probed using stimulus intensities at or above 150% of resting motor threshold (RMT). In contrast, facilitation of MEPs following iTBS was strongest and most consistent at 110% of RMT. Conclusions: The plasticity response to both cTBS and iTBS is influenced by the stimulus intensity used to probe the induced changes in corticospinal excitability. [ABSTRACT FROM AUTHOR]

The primary somatosensory cortex (SI) plays a critical role in somatosensation as well as in action performance and social cognition. Although the SI has been a major target of experimental and clinical research using non-invasive transcranial magnetic stimulation (TMS), to date information on the effect of TMS over the SI on its resting-state functional connectivity is very scant. Here, we explored whether continuous theta burst stimulation (cTBS), a repetitive TMS protocol, administered over the SI can change the functional connectivity of the brain at rest, as measured using resting-state functional magnetic resonance imaging (rs-fMRI). In a randomized order on two different days we administered active TMS or sham TMS over the left SI. TMS was delivered off-line before scanning by means of cTBS. The target area was selected previously and individually for each subject as the part of the SI activated both when the participant executes and observes actions. Three analytical approaches, both theory driven (partial correlations and seed based whole brain regression) and more data driven (Independent Component Analysis), indicated a reduction in functional connectivity between the stimulated part of the SI and several brain regions functionally associated with the SI including the dorsal premotor cortex, the cerebellum, basal ganglia, and anterior cingulate cortex. These findings highlight the impact of cTBS delivered over the SI on its functional connectivity at rest. Our data may have implications for experimental and therapeutic applications of cTBS over the SI. [ABSTRACT FROM AUTHOR]

The perception of physical effort is relatively unaffected by the suppression of sensory afferences, indicating that this function relies mostly on the processing of the central motor command. Neural signals in the supplementary motor area (SMA) correlate with the intensity of effort, suggesting that the motor signal involved in effort perception could originate from this area, but experimental evidence supporting this view is still lacking. Here, we tested this hypothesis by disrupting neural activity in SMA, in primary motor cortex (M1), or in a control site by means of continuous theta-burst transcranial magnetic stimulation, while measuring effort perception during grip forces of different intensities. After each grip force exertion, participants had the opportunity to either accept or refuse to replicate the same effort for varying amounts of reward. In addition to the subjective rating of perceived exertion, effort perception was estimated on the basis of the acceptance rate, the effort replication accuracy, the influence of the effort exerted in trial t on trial t+1, and pupil dilation. We found that disruption of SMA activity, but not of M1, led to a consistent decrease in effort perception, whatever the measure used to assess it. Accordingly, we modeled effort perception in a structural equation model and found that only SMA disruption led to a significant alteration of effort perception. These findings indicate that effort perception relies on the processing of a signal originating from motor-related neural circuits upstream of M1 and that SMA is a key node of this network. [ABSTRACT FROM AUTHOR]

Objective The present study investigated the effects of continuous theta-burst stimulation (cTBS) over primary somatosensory (SI) and motor (M1) cortices on motor-evoked potentials (MEPs) and short-latency afferent inhibition (SAI). Methods MEPs and SAI were recorded from the first dorsal interosseous (FDI) muscle of the right hand following 30 Hz cTBS over left-hemisphere SI and M1 delivered to the same participants in separate sessions. Measurements were taken before and up to 60 min following cTBS. Results CTBS over M1 suppressed MEPs and did not alter SAI. In contrast cTBS over SI facilitated MEPs and decreased median and digital nerve evoked SAI. Conclusions These findings indicate that SAI amplitude is influenced by cTBS over SI but not M1, suggesting an important role for SI in the modulation of this circuit. These data provide further evidence that cTBS over SI versus M1 has opposite effects on corticospinal excitability. Significance To date, plasticity-inducing TMS protocols delivered over M1 have failed to modulate SAI, and the present research continues to support these findings. However, in young adults, cTBS over SI acts to reduce SAI and simultaneously increase corticospinal excitability. Future studies may investigate the potential to modulate SAI via targeting neural activity within SI. [ABSTRACT FROM AUTHOR]

A cerebellar role in spatial information processing has been advanced even in the absence of physical manipulation, as occurring in mental rotation. The present study was aimed at investigating the specific involvement of left and right cerebellar hemispheres in two tasks of mental rotation. We used continuous theta burst stimulation to downregulate cerebellar hemisphere excitability in healthy adult subjects performing two mental rotation tasks: an Embodied Mental Rotation (EMR) task, entailing an egocentric strategy, and an Abstract Mental Rotation (AMR) task entailing an allocentric strategy. Following downregulation of left cerebellar hemisphere, reaction times were slower in comparison to sham stimulation in both EMR and AMR tasks. Conversely, identical reaction times were obtained in both tasks following right cerebellar hemisphere and sham stimulations. No effect of cerebellar stimulation side was found on response accuracy. The present findings document a specialization of the left cerebellar hemisphere in mental rotation regardless of the kind of stimulus to be rotated. [ABSTRACT FROM AUTHOR]

Continuous theta burst stimulation (cTBS) is a technique that allows for altering of brain activity. Research to date has focused on the effect of cTBS on the target area, but less is known about its effects on the resting state functional connectivity between different brain regions. We investigated this issue by applying cTBS to the occipital cortex and probing its influence in retinotopically defined regions in early visual cortex using functional MRI. We found that occipital cTBS reliably decreased the resting state functional connectivity (i.e., the correlation of spontaneous activity) between regions of the early visual cortex. In the context of a perceptual task, such an effect could mean that cTBS affects the strength of the perceptual signal, its variability, or both. We investigated this issue in a second experiment in which subjects performed a perceptual discrimination task and indicated their level of certainty on each trial. The results showed that occipital cTBS decreased both subjects' accuracy and confidence. Signal detection modeling suggested that these impairments resulted primarily from a decreased strength of the perceptual signal, with a nonsignificant trend of a decrease in signal variability. We discuss the implications of these experiments for understanding the mechanisms by which cTBS influences brain activity and perceptual processes. [ABSTRACT FROM AUTHOR]

Bisphthalamic acids were prepared by reaction of phthalic anhydride and aliphatic diamines. Flame retardant poly(ester-amide)s were prepared by reaction of brominated epoxy resin with bisphthalamic acids and post reaction was carried out with acryloyl chloride to obtained acrylated flame retardant poly(ester-amide) resins. Bismaleimides were prepared by reaction between aromatic diamines and maleic anhydride. Carboxy terminated bismaleimides were prepared by Michael addition reaction of bismaleimides and 4-amino benzoic acid. Flame retardant poly(ester-imide)s were prepared by reaction between carboxy terminated bismaleimides and brominated epoxy resin. All the obtained products were characterized and analyzed by making composites. [ABSTRACT FROM AUTHOR]

Aggressive behavior is aimed at causing damage or pain to another individual. Aggression has been associated with structural and functional deficits in numerous brain areas, including the dorsolateral region of the prefrontal cortex (DLPFC), typically related to inhibition and impulse control. In this study, we used inhibitory continuous theta-burst magnetic stimulation (cTBS) to explore the role of the right and left DLPFC in aggression. Sixteen healthy right-handed volunteers underwent two sessions involving random, real and sham, right and left DLPFC stimulations. These sessions were followed by theSocial Orientation Paradigm(SOP), a monetary task that was specially designed to assess participants' aggressive tendencies by measuring the patterns of theirreactive aggression(a response to a perceived provocation) andproactive aggression(an aggressive act with goal-oriented purposes). Results indicate that using cTBS to target the left DLPFC was associated with a greater increase in aggressive responses than right DLPFC stimulation. This pattern of results was found for both reactive and proactive types of aggressive reactions. It is concluded that DLPFC asymmetry is involved in modulating reactive and proactive aggression. Our results are in line with recent studies suggesting that the left DLPFC plays a major role in aggressive behavior. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation ( TMS) is a useful tool to induce and measure plasticity in the human brain. However, the cortical effects are generally indirectly evaluated with motor-evoked potentials ( MEPs) reflective of modulation of cortico-spinal excitability. In this study, we aim to provide direct measures of cortical plasticity by combining TMS with electroencephalography ( EEG). Continuous theta-burst stimulation ( cTBS) was applied over the primary motor cortex ( M1) of young healthy adults, and we measured modulation of (i) MEPs, (ii) TMS-induced EEG evoked potentials ( TEPs), (iii) TMS-induced EEG synchronization and (iv) eyes-closed resting EEG. Our results show the expected cTBS-induced decrease in MEP size, which we found to be paralleled by a modulation of a combination of TEPs. Furthermore, we found that cTBS increased the power in the theta band of eyes-closed resting EEG, whereas it decreased single-pulse TMS-induced power in the theta and alpha bands. In addition, cTBS decreased the power in the beta band of eyes-closed resting EEG, whereas it increased single-pulse TMS-induced power in the beta band. We suggest that cTBS acts by modulating the phase alignment between already active oscillators; it synchronizes low-frequency (theta and/or alpha) oscillators and desynchronizes high-frequency (beta) oscillators. These results provide novel insight into the cortical effects of cTBS and could be useful for exploring cTBS-induced plasticity outside of the motor cortex. [ABSTRACT FROM AUTHOR]

Most neuroimaging studies on planning report bilateral activations of the dorsolateral prefrontal cortex (dlPFC). Recently, these concurrent activations of left and right dlPFC have been shown to double dissociate with different cognitive demands imposed by the planning task: Higher demands on the extraction of task-relevant information led to stronger activation in left dlPFC, whereas higher demands on the integration of interdependent information into a coherent action sequence entailed stronger activation of right dlPFC. Here, we used continuous theta-burst stimulation (cTBS) to investigate the supposed causal structure-function mapping underlying this double dissociation. Two groups of healthy subjects (left-lateralized stimulation, n = 26; right-lateralized stimulation, n = 26) were tested within-subject on a variant of the Tower of London task following either real cTBS over dlPFC or sham stimulation over posterior parietal cortex. Results revealed that, irrespective of specific task demands, cTBS over left and right dlPFC was associated with a global decrease and increase, respectively, in initial planning times compared to sham stimulation. Moreover, no interaction between task demands and stimulation type (real vs. sham) and/or stimulation side (left vs. right hemisphere) were found. Together, against expectations from previous neuroimaging data, lateralized cTBS did not lead to planning-parameter specific changes in performance, but instead revealed a global asymmetric pattern of faster versus slower task processing after left versus right cTBS. This global asymmetry in the absence of any task-parameter specific impact of cTBS suggests that different levels of information processing may span colocalized, but independent axes of functional lateralization in the dlPFC. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The application of repetitive transcranial magnetic stimulation (rTMS) in bursts at theta frequencies (TBS) may produce lasting neuroplastic changes in the human cortex. However, there exists high variability in subjects’ responses, possibly due to non-optimal stimulation characteristics. Here we compare the efficacy of two variations of continuous TBS (cTBS) for producing neuroplastic change in the human primary motor cortex (M1). Methods: The two cTBS paradigms were: (1) standard cTBS (cTBSstd) (three stimuli at 50Hz, repeated at 5Hz), and (2) modified cTBS (cTBSmod) (three stimuli at 30Hz, repeated at 6Hz with intensity). Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle before, as well as at 0, 5, 10, 20 and 30min following each paradigm. Results: Both cTBSstd (P =0.05) and cTBSmod (P <0.0001) induced a suppression of MEP amplitudes. However, MEP suppression following cTBSmod was greater (ANOVARM; P =0.02). Experiments using magnetic brainstem stimulation provided evidence that cTBSmod induced MEP suppression through cortical mechanisms. Conclusions: The neuroplastic response of the human M1 to cTBS is highly dependent on the stimulation parameters employed. Significance: These findings may have significant implications for the clinical application of cTBS paradigms. [Copyright &y& Elsevier]

There is some limited evidence suggesting that the spaced application of repetitive transcranial magnetic stimulation (rTMS) protocols may extend the duration of induced neuroplastic changes. However, this has yet to be demonstrated in the human primary motor cortex (M1). We evaluated whether the paired application of an inhibitory rTMS protocol [continuous theta burst stimulation (cTBS)] at 10-min intervals prolonged the duration of induced M1 plasticity. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle before and following single and paired cTBS protocols applied with two intensities: 80% of active motor threshold (AMT80) and 70% of resting motor threshold (RMT70). Single cTBS protocols did not significantly influence MEP amplitudes. Whereas paired trains applied at AMT80 had no effect on MEP amplitudes, paired cTBS trains at RMT70 significantly reduced them. MEP amplitudes remained suppressed for at least 2 h following the second train. Control experiments suggested that the contraction used to establish active motor threshold prior to cTBS application may be responsible for blocking the effect of paired cTBS trains at AMT80. The results suggest that the spaced application of cTBS protocols may be an effective approach for establishing long-lasting M1 neuroplasticity only in the absence of prior voluntary motor activation. These findings may have important implications for the therapeutic application of rTMS. [ABSTRACT FROM AUTHOR]

Background: Rapid compensatory arm reactions represent important response strategies following an unexpected loss of balance. While it has been assumed that early corrective actions arise largely from sub-cortical networks, recent findings have prompted speculation about the potential role of cortical involvement. To test the idea that cortical motor regions are involved in early compensatory arm reactions, we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants prior to evoking upper limb balance reactions in response to whole body perturbation. We hypothesized that following cTBS to the M1 hand area evoked EMG responses in the stimulated hand would be diminished. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair while holding a stable handle with both hands. The chair was held vertical by a magnet and was triggered to fall backward unpredictably. To regain balance, participants used the handle to restore upright stability as quickly as possible with both hands. Muscle activity was recorded from proximal and distal muscles of both upper limbs. Results: Our results revealed an impact of cTBS on the amplitude of the EMG responses in the stimulated hand muscles often manifest as inhibition in the stimulated hand. The change in EMG amplitude was specific to the target hand muscles and occasionally their homologous pairs on the non-stimulated hand with no consistent effects on the remaining more proximal arm muscles. Conclusions: Present findings offer support for cortical contributions to the control of early compensatory arm reactions following whole-body perturbation. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Somatosensory evoked potentials (SEPs) were used to index somatosensory–somatosensory interhemispheric interactions and highlight potential mechanisms by which TMS alters contralateral somatosensory cortex excitability. Methods: Fifteen healthy individuals participated in three sessions on separate days. On each day participants received either: (1) continuous theta burst (cTBS), (2) 1Hz repetitive transcranial magnetic stimulation (rTMS) or (3) control TMS over left somatosensory cortex. SEPs from right somatosensory cortex were recorded before and after TMS while participants were at rest, performed sensorimotor tracking or the sustained attention to response task (SART). Left-handed tracking performance was also indexed. Results: N20–P27 amplitude was increased following 1Hz rTMS while participants were at rest. This increased amplitude was not observed during right-handed tracking or the SART. N20–P27 amplitude was not influenced by cTBS or control TMS. P15–N20 and N34–P50 SEP components were not influenced by TMS. Right- and left-handed tracking performance was not transiently influenced by TMS. Conclusions: The results support TMS induced somatosensory–somatosensory interactions and offer converging evidence for an intercortical, rather that intracortical, mechanism that mediates contralateral sensory processing. These interactions appear to be dependent on concurrent attention/task demands. Significance: Somatosensory–somatosensory interactions are reflected by intercortical mechanisms that are state and task dependent. [Copyright &y& Elsevier]

Background: Because standard repetitive transcranial magnetic stimulation (rTMS) protocols exhibit post-stimulus effects of short duration, novel protocols such as theta burst stimulation (TBS), are promising approaches to enhance the effectiveness of rTMS. However, little is known about the side effect profile of such protocols. Thus, the present study explores whether TBS is safe particularly in terms of effects on cognition, mood, and electroencephalogram (EEG) measures in healthy subjects. Methods: Twenty-four healthy volunteers participated in 2 randomized, placebo-controlled, cross-over experiments and underwent continuous TBS (cTBS), intermittent TBS (iTBS), and shamTBS either over the left dorsolateral prefrontal cortex (DLPFC, n = 12) or the medial prefrontal cortices (mPFC, n = 12). Clinical side effects, performance in a neuropsychological battery, mood changes, and resting EEG were recorded. Results: Neither a seizure nor epileptiform EEG activity was observed. The most prominent side effect was the occurrence of vagal reactions during TBS; otherwise no serious side effects were found. Standardized low-resolution brain electromagnetic tomography showed current density changes in the α2 band after iTBS of the DLPFC, which remained detectable up to 50 min after stimulation. The few changes in neuropsychological performance were concordant with stimulation site. No impact on mood was detected. Conclusions: Although TBS protocols of the human prefrontal cortex seem to be safe in healthy subjects, future studies need to address the occurrence of vagal reactions. Excitatory and inhibitory properties of motor cortex TBS might not be transferable to prefrontal sites, and the action of specific TBS protocols needs to be further investigated prior to clinical application. [Copyright &y& Elsevier]

Introduction: Around 25-30% of subjects with auditory verbal hallucinations(AVH) in schizophrenia are resistant to antipsychotic treatment. Continuous theta-burst stimulation(cTBS) is a protocol of rTMS(repetitive Transcranial Magnetic Stimulation) which is a continuous un-interrupted stimulus train that induces long-term depression-like effects. A stimulation protocol with cTBS for AVH has shown varying results in different trails. We tested cTBS as a treatment strategy for refractory AVH in a Singleblind, sham-controlled trial. Objectives: This study aimed to evaluate the efficacy of cTBS on bilateral TPJ for the treatment-resistant AVH. Methods: Out of seventy patients who were screened, sixteen patients met eligibility criteria and were randomly allocated to cTBS or sham group. They received cTBS or sham treatments over bilateral TPJ twice daily for 12 days. The severity of AVH was assessed independently by blind raters with Auditory Hallucinations Rating Scale(AHRS) at baseline, after completion of treatment and two weeks later. Results: One patient dropped out of the study before completion. In the remaining fifteen, AVH improved in both the groups as measured with AHRS after treatment. However, there was no significant difference between the cTBS and sham group. There were no adverse effects. Conclusions: cTBS intervention showed no specific benefit in treating resistant auditory hallucinations. The effects were general rather than specific to cTBS. Future research should evaluate cTBS as an add-on treatment in schizophrenia without keeping the selection criteria of treatment-resistance as rigid, thereby evaluating the speedier response and thereby increasing the overall efficacy of the combined treatment approach to AVH. [ABSTRACT FROM AUTHOR]

Microsaccade is a type of fixational eye movements that is modulated by various sensory and cognitive processes, and impact our visual perception. Although studies in monkeys have demonstrated a functional role for the superior colliculus and frontal eye field (FEF) in controlling microsaccades, our understanding of the neural mechanisms underlying the generation of microsaccades is still limited. By applying continuous theta-burst stimulation (cTBS) over the right FEF and the vertex, we investigated the role of the FEF in generating human microsaccade responses evoked by salient stimuli or by changes in background luminance. We observed higher microsaccade rates prior to target appearance, and larger rebound in microsaccade occurrence following salient stimuli, when disruptive cTBS was applied over FEF compared to vertex stimulation. Moreover, the microsaccade direction modulation after changes in background luminance was disrupted with FEF stimulation. Together, our results constitute the first evidence of FEF modulation in human microsaccade responses. • We examined the role of the frontal eye field (FEF) in human microsaccade responses using continuous theta-burst stimulation. • Higher microsaccade rates prior to target appearance were observed in FEF, compared to, vertex stimulation. • Larger rebound in microsaccade occurrence following salient stimuli was obtained with FEF stimulation. • The microsaccade direction modulation after background luminance changes was disrupted with FEF stimulation. • The FEF is involved in the control of human microsaccade generation. [ABSTRACT FROM AUTHOR]

Although it is well established that fronto-parietal regions are active during action observation, whether they play a causal role in the ability to infer others' intentions from visual kinematics remains undetermined. In the experiments reported here, we combined offline continuous theta burst stimulation (cTBS) with computational modeling to reveal and causally probe single-trial computations in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Participants received cTBS over the left anterior IPL and the left IFG pars orbitalis in separate sessions before completing an intention discrimination task (discriminate intention of observed reach-to-grasp acts) or a kinematic discrimination task unrelated to intention (discriminate peak wrist height of the same acts). We targeted intention-sensitive regions whose fMRI activity, recorded when observing the same reach-to-grasp acts, could accurately discriminate intention. We found that transient disruption of activity of the left IPL, but not the IFG, impaired the observer's ability to attribute intention to action. Kinematic discrimination unrelated to intention, in contrast, was largely unaffected. Computational analyses of how encoding (mapping of intention to movement kinematics) and readout (mapping of kinematics to intention choices) intersect at the single-trial level revealed that IPL cTBS did not diminish the overall sensitivity of intention readout to movement kinematics. Rather, it selectively misaligned intention readout with respect to encoding, deteriorating mapping from informative kinematic features to intention choices. These results provide causal evidence of how the left anterior IPL computes mapping from kinematics to intentions. • Perturbation of inferior parietal lobule (IPL) impairs intention to action mapping • Inferior frontal gyrus perturbation does not affect intention reading • Observers can still discriminate changes in kinematics after IPL perturbation • IPL perturbation selectively misaligns intention readout to intention encoding Patri et al. combine continuous theta burst stimulation (cTBS) with computational modeling to causally probe single-trial intention computations in fronto-parietal regions. They find that stimulation over the inferior parietal lobule deteriorates mapping from informative kinematic features to intention choices during action observation. [ABSTRACT FROM AUTHOR]

Long-term depression (LTD) is a form of physiologic plasticity that is important for reversal learning and may be linked to major depression. Few studies have examined LTP-like plasticity in patients with depression. It is unclear if continuous theta burst stimulation (cTBS) induced LTD is altered in depression patients. Here we recruited 29 healthy control subjects and 31 female patients with depression. We performed cTBS protocol on left motor cortex and employed motor evoked potentials (MEPs) response to measure LTD-like plasticity. Peripheral molecules were measured for correlation analyses to cortical plasticity. Our results revealed persistent LTD-like plasticity deficits in female patients with depression. LTD-like plasticity was impaired in patients with depression despite the fact that peripheral concentrations of BDNF were comparable to that of healthy subjects. Conclusions: Our findings provide evidence for impaired LTD-like plasticity in patients with depression which may be an important mechanism linked to the pathophysiology and treatment of this disorder. • Our results revealed persistent LTD-like plasticity deficits in female patients with depression. • LTD-like plasticity was impaired in MDD despite the fact that BDNF were comparable to that of healthy subjects. • Impaired LTD-like plasticity may an important mechanism linked to the pathophysiology and treatment of this disorder. [ABSTRACT FROM AUTHOR]

• cTBS modulates the excitability of pyramidal neuron in cortex by enhancing phasic inhibition. • In chronic phase of stroke, phasic inhibition is elevated while glutamate-mediated excitatory signaling remains normal. • In chronic phase of stroke, the enhanced phasic inhibition by cTBS promotes stroke recovery. Continuous theta burst stimulation (cTBS) has been widely recognized as a therapeutic treatment for ischemic stroke, but the underlying mechanism is still elusive. Here, we investigated the protective effects of cTBS in the posterior parietal cortex during the chronic phase of stroke in the photothrombotic ischemic model. Infarction volume and neuron excitability in the peri-infarct area were assessed using immunohistochemistry and whole-cell patch-clamp. Spatial cognitive function was measured using the Morris water maze. Gamma-Amino butyric acid (GABA) interneurons were responsive to cTBS, and cTBS induced elevated phasic inhibition rather than tonic inhibition. Given that GABA -A -mediated phasic inhibition was elevated during the chronic phase of ischemic stroke for 30 days and was beneficial for stroke recovery, we investigated the therapeutic potential of cTBS in promoting functional recovery and found that the elevated phasic inhibition by cTBS improved spatial cognitive function in the photothrombotic stroke mouse model with induction in the posterior parietal cortex. Our study indicates the mechanism by which cTBS may modify the excitability of the brain cortex and provides novel insight into the potential of cTBS to protect against neuronal dysfunction in ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective Continuous tetha burst stimulation (cTBS) protocol mainly consists of 3 stimulus bursts repeating every 200 ms at 50 Hz and It has been interpreted that cTBS had inhibitory effects on human motor cortex. On the other hand, there are some reports that 50 Hz cTBS had variability within and between subjects on cortical excitability. In addition, little was known about the effect of different cTBS modalities. The objective of this study is to investigate the effects of 50 Hz, 30 Hz and 100 Hz cTBS on motor cortical excitability healthy subjects. Method Resting motor treshold (rMT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and motor evoked potential (MEP) amplitude were studied in 30 healthy subjects. Conditioning stimuli was 80% of rMT and test stimuli was 120% of rMT during SICI and ICF studies. rMT, MEP, SICI and ICF tests were repeated at just after and 30 min later than first 30, 50 and 100 Hz cTBS studies. Results In consistent with the current literature 50 Hz cTBS has inhibitory effects on MEP responses. 30 Hz cTBS has more greater inhibition than 50 Hz cTBS. On the other hand 100 Hz cTBS has facilitatory effects on cortical excitability. Discussion The effects of cTBS on motor cortical excitability depend on the studied paradigm. These results should be considered for selection of the research protocols or therapeutic application of cTBS. [ABSTRACT FROM AUTHOR]